Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An intriguing problem of diabetes mellitus is the development of generalized angiopathy and concomitant hypertension. However, there is still a controversy whether beta-adrenoceptor antagonists can be used as antihypertensive agents in diabetes. Four groups of rats were investigated: nondiabetic controls, diabetes mellitus, diabetes + celiprolol (250 mg/kg body weight/day), diabetes + metoprolol (125 mg/kg body weight/day) after 6 months. Diabetes was induced by i.v. streptozotocin injection. We examined vascular structure and function histologically and by an in vitro microvideoangiometry of isolated perfused mesenterium. Additionally, we investigated the effects of hyperglycemia and celiprolol on NO release in cultivated aortic endothelial cells and the effect of celiprolol on transendothelial paracellular permeability. Diabetes resulted in endothelial dysfunction, characterized by a reduced response to acetylcholine and L-N(G)-nitro-arginine and an unchanged response to sodium nitroprusside (SNP). These effects were significantly antagonized by celiprolol but were not influenced by metoprolol treatment. This was supported by the finding of typical vascular changes associated with diabetes like media thickening, reduced cardiac capillary/muscle fiber ratio, and glomerulosclerosis, which were significantly reduced by celiprolol but not influenced by metoprolol treatment. Ketonuria improved after celiprolol treatment, whereas blood glucose, lipids, and body weight were not different between the diabetic groups. In cultured cells, celiprolol did not induce direct NO release but reversed the impairment of stimulated NO release caused by hyperglycemia. Furthermore, celiprolol reduced endothelial paracellular permeability. We conclude that celiprolol can exert antiangiopathic effects in diabetic rats and that both beta-adrenoceptor antagonists did not aggravate diabetic angiopathy and metabolic derangement.
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PMID:Different effects of the beta-adrenoceptor antagonists celiprolol and metoprolol on vascular structure and function in long-term type I diabetic rats. 1002 26

MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) is a maternally inherited disorder characterized by recurrent cerebral infarctions that do not conform to discreet vascular territories. Here we report on a patient who presented at 7 years of age with loss of consciousness and severe metabolic acidosis following vomiting and dehydration. She developed progressive sensorineural hearing loss, myopathy, ptosis, short stature, and mild developmental delays after normal early development. Biochemical testing identified metabolites characteristic of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (hexanoylglycine and suberylglycine), but also severe lactic acidemia (10-25 mM) and, in urine, excess of lactic acid, intermediates of the citric cycle, and marked ketonuria, suggesting mitochondrial dysfunction. She progressed rapidly to develop temporary cortical blindness. Brain imaging indicated generalized atrophy, more marked on the left side, in addition to white matter alterations consistent with a mitochondrial disorder. Magnetic resonance angiography indicated occlusion of the left cerebral artery with development of collateral circulation (Moyamoya syndrome). This process worsened over time to involve the other side of the brain. A muscle biopsy indicated the presence of numerous ragged red fibers. Molecular testing confirmed compound heterozygosity for the common mutation in the MCAD gene (985A>G) and a second pathogenic mutation (233T>C). MtDNA testing indicated that the muscle was almost homoplasmic for the 3243A>T mutation in tRNALeu, with a lower mutant load (about 50% heteroplasmy) in blood and skin fibroblasts. These results indicate that mitochondrial disorders may be associated with severe vascular disease resulting in Moyamoya syndrome. The contribution of the concomitant MCAD deficiency to the development of the phenotype in this case is unclear.
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PMID:Progressive cerebral vascular degeneration with mitochondrial encephalopathy. 1820 88